Ionizing radiation is capable of producing several kinds of biological end results, including mutation and cell death. In spite of these possible detrimental effects on biological systems, radiation is being used both as a diagnostic tool in medicine and as a therapeutic tool in cancer treatment. The goal of this project is to further understand the interaction of ionizing radiation with the DNA molecule. This molecule is chosen for study because of its central and critical role in maintaining the genetic integrity of the cell. The research is designed to study the physical damage in DNA as expressed by scission of the DNA strand, and to correlate this response with damage to the biological activity of the DNA molecule. A replicative intermediate in the synthesis of bacteriophage phi X174 DNA will be used in this research. Two ideal properties of this molecule are, first, it is a supercoiled molecule and thus allows sensitive analysis for strand breaks, and second, it is a complete genome and has biological activity, thus allowing analysis for biological damage. The biological damage is undoubtedly a result of physicochemical changes induced in the DNA by energy released from the ionizing radiation. Because strand breaks represent a type of physicochemical damage, and can be measured with a minimum of manipulation following irradiation and without chemical treatment (which could aggravate the radiation damage in an unidentifiable fashion), the production of strand breaks will be used as the standard measure for physiocochemical damage. Irradiation will be in a controlled environment so that secondary factors affecting radiation response can be evaluated. Appropriate radical scavengers will be used in order to elucidate the role of water radicals in radiation damage to DNA. Radiation sensitive mutants of the bacterial cells for the biological assay will be used in order to ascertain which biological repair systems are effective in the recovery of the DNA from biological damage. The eventual goal of this project is to determine the fundamentals of radiation action of DNA with particular emphasis on the mechanisms of radiation induced biological damage in the DNA.